A Pilot Study Using Autologous Regulatory T Cell Infusion Zortress (Everolimus) in Renal Transplant Recipients
| Status: | Recruiting |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - 65 |
| Updated: | 3/9/2019 |
| Start Date: | August 2019 |
| End Date: | December 31, 2019 |
Tolerance Induction Using Autologous Regulatory T Cell Infusion and Zortress (Everolimus) in Renal Transplant Recipients: a Pilot Study
This study will enroll individuals who have end stage renal disease and who are undergoing a
solitary kidney transplant. This study is investigating/evaluating the safety and
effectiveness of collecting, expanding and infusing a specific certain type of immune cell
known as Regulatory T cells (Treg cells) to renal transplant recipients who are using
Zortress (Everolimus) as immunosuppressive therapy.
Treg cells, once they have been expanded in the laboratory to help prevent kidney rejection.
Treg cells are collected from a participant's blood through a procedure called apheresis.
Treg cells are a type of white blood cells that are able to suppress the activity of other
immune cells responsible for organ rejection. The investigator plans to enroll 12
participants at the University of Kentucky.
solitary kidney transplant. This study is investigating/evaluating the safety and
effectiveness of collecting, expanding and infusing a specific certain type of immune cell
known as Regulatory T cells (Treg cells) to renal transplant recipients who are using
Zortress (Everolimus) as immunosuppressive therapy.
Treg cells, once they have been expanded in the laboratory to help prevent kidney rejection.
Treg cells are collected from a participant's blood through a procedure called apheresis.
Treg cells are a type of white blood cells that are able to suppress the activity of other
immune cells responsible for organ rejection. The investigator plans to enroll 12
participants at the University of Kentucky.
The purpose of this research study is to learn alternative ways to control the body's immune
responses after renal transplantation. The investigator's goal is to prevent or reduce the
side-effects of long-term immunosuppressive therapy.
By doing this study, the investigator hopes to learn how safe and effective infusing
autologous Treg cells, after renal transplantation, to renal transplant recipients who are
taking Zortress (Everolimus) to control the immune response.
Individuals who decide to take part in this research study and are eligible to start, will be
followed for 1 year after their transplant. The research procedures will be conducted at the
University of Kentucky Medical Center and require nine study visits. One of the study visits
requires an overnight stay. Participants will be admitted to the University of Kentucky
Center for Clinical and Translational Science (CCTS) inpatient research unit for this study
visit. Depending on the frequency of an participant's post-transplant clinic visits, some of
the study visits could be done at the same time as their regular clinic visits. If not, they
will occur in the transplant clinic or in the University of Kentucky Center for Clinical and
Translational Science (CCTS) outpatient research unit.
The total amount of time required for participation in the study will be up to 40 hours over
1 year. The total amount of blood taken for the study will be about 14 tablespoons (200ml/6.5
ounces) over 1 year.
STUDY PROCEDURES:
Blood Samples: These will be collected via a needle inserted into a vein in the arm.
Human immunodeficiency virus (HIV) and hepatitis testing: Test for HIV, Hepatitis B and
Hepatitis C will be done as part of the participant's routine transplant evaluation. The
results from these tests will be used to determine study eligibility at the pre-transplant
study visit.
If any of these tests are positive, a qualified person will provide counseling to the
participant. The State of Kentucky requires that researchers must report HIV, Hepatitis B and
Hepatitis C positive test results to the local health department serving the jurisdiction in
which the participant resides, and that the information reported must include the
participant's full name, address, phone number, county of residence, and applicable
disease/condition.
Apheresis: Apheresis is a procedure in which a machine receives blood removed from a
participant's body and separates it into its various components: plasma, platelets, white
blood cells and red blood cells. This procedure is done in the Apheresis Center in the Gill
Heart Building at the UK Chandler Hospital. Depending on the reason for apheresis, one of
these components is isolated and collected by the instrument, while the others are re-infused
to the body.
In this particular research study the investigator is going to collect white blood cells to
isolate Treg cells for expansion. The process of collecting white blood cells will take
approximately 90 minutes. Once the blood cells are collected, the research team will isolate
the Treg cells. These cells will be cultured in the laboratory under special conditions and
will be expanded. After approximately 3 weeks in culture, the cells will have increased in
number and be ready for the autologous Treg cell infusion.
Autologous Treg cell infusion: This will be a single intravenous (IV) infusion. A standard IV
line will be started in a vein of the arm. The participant's own expanded regulatory T cells
will be added to a sterile infusion solution, called Albumin, and administered to to the
participant, and the infusion will take about 3 to 4 hours. Participant's vital signs will be
monitored before, during, and after the infusion.
Renal Biopsy: Two renal biopsies (removal of a piece of kidney tissue) will be performed. The
first one will be done in the operating room during the participant's renal transplant
surgery. The biopsy will come from the new kidney prior to being transplanted. The second one
will be done 6 weeks after the autologous Treg cell infusion and will be compared to the
first one. The second renal biopsy is optional. If a participant agrees to the second biopsy
it will be done as an outpatient procedure in the radiology department at the University of
Kentucky. Using an ultrasound for guidance, the investigator will pass a larger needle
through the skin to obtain a small sample of the transplanted kidney.
Physical Examination and Vital Sign Measurement: These will be done by a member of the study
team. The participant's body temperature, heart rate, respiratory rate, and blood pressure
will be measured and recorded.
Pregnancy Tests: A pregnancy test will be performed on women who could be pregnant prior to
beginning the study and again prior to receiving the autologous Treg cell infusion to exclude
the possibility of pregnancy. For study purposes women who could become pregnant must use two
effective contraceptive starting prior to renal transplant through to visit 9.
responses after renal transplantation. The investigator's goal is to prevent or reduce the
side-effects of long-term immunosuppressive therapy.
By doing this study, the investigator hopes to learn how safe and effective infusing
autologous Treg cells, after renal transplantation, to renal transplant recipients who are
taking Zortress (Everolimus) to control the immune response.
Individuals who decide to take part in this research study and are eligible to start, will be
followed for 1 year after their transplant. The research procedures will be conducted at the
University of Kentucky Medical Center and require nine study visits. One of the study visits
requires an overnight stay. Participants will be admitted to the University of Kentucky
Center for Clinical and Translational Science (CCTS) inpatient research unit for this study
visit. Depending on the frequency of an participant's post-transplant clinic visits, some of
the study visits could be done at the same time as their regular clinic visits. If not, they
will occur in the transplant clinic or in the University of Kentucky Center for Clinical and
Translational Science (CCTS) outpatient research unit.
The total amount of time required for participation in the study will be up to 40 hours over
1 year. The total amount of blood taken for the study will be about 14 tablespoons (200ml/6.5
ounces) over 1 year.
STUDY PROCEDURES:
Blood Samples: These will be collected via a needle inserted into a vein in the arm.
Human immunodeficiency virus (HIV) and hepatitis testing: Test for HIV, Hepatitis B and
Hepatitis C will be done as part of the participant's routine transplant evaluation. The
results from these tests will be used to determine study eligibility at the pre-transplant
study visit.
If any of these tests are positive, a qualified person will provide counseling to the
participant. The State of Kentucky requires that researchers must report HIV, Hepatitis B and
Hepatitis C positive test results to the local health department serving the jurisdiction in
which the participant resides, and that the information reported must include the
participant's full name, address, phone number, county of residence, and applicable
disease/condition.
Apheresis: Apheresis is a procedure in which a machine receives blood removed from a
participant's body and separates it into its various components: plasma, platelets, white
blood cells and red blood cells. This procedure is done in the Apheresis Center in the Gill
Heart Building at the UK Chandler Hospital. Depending on the reason for apheresis, one of
these components is isolated and collected by the instrument, while the others are re-infused
to the body.
In this particular research study the investigator is going to collect white blood cells to
isolate Treg cells for expansion. The process of collecting white blood cells will take
approximately 90 minutes. Once the blood cells are collected, the research team will isolate
the Treg cells. These cells will be cultured in the laboratory under special conditions and
will be expanded. After approximately 3 weeks in culture, the cells will have increased in
number and be ready for the autologous Treg cell infusion.
Autologous Treg cell infusion: This will be a single intravenous (IV) infusion. A standard IV
line will be started in a vein of the arm. The participant's own expanded regulatory T cells
will be added to a sterile infusion solution, called Albumin, and administered to to the
participant, and the infusion will take about 3 to 4 hours. Participant's vital signs will be
monitored before, during, and after the infusion.
Renal Biopsy: Two renal biopsies (removal of a piece of kidney tissue) will be performed. The
first one will be done in the operating room during the participant's renal transplant
surgery. The biopsy will come from the new kidney prior to being transplanted. The second one
will be done 6 weeks after the autologous Treg cell infusion and will be compared to the
first one. The second renal biopsy is optional. If a participant agrees to the second biopsy
it will be done as an outpatient procedure in the radiology department at the University of
Kentucky. Using an ultrasound for guidance, the investigator will pass a larger needle
through the skin to obtain a small sample of the transplanted kidney.
Physical Examination and Vital Sign Measurement: These will be done by a member of the study
team. The participant's body temperature, heart rate, respiratory rate, and blood pressure
will be measured and recorded.
Pregnancy Tests: A pregnancy test will be performed on women who could be pregnant prior to
beginning the study and again prior to receiving the autologous Treg cell infusion to exclude
the possibility of pregnancy. For study purposes women who could become pregnant must use two
effective contraceptive starting prior to renal transplant through to visit 9.
Inclusion Criteria:
- Fluent in English able to understand and provide informed consent
- End stage renal disease listed for primary solitary kidney transplant
- Willing to participate in the study and comply with study requirements
- Female participants must agree to use 2 different birth control methods
Exclusion Criteria:
- History of previous organ, tissue or cell transplant
- Known sensitivity to Sirolimus, Everolimus, Tacrolimus or MMF
- Previous chronic use of systemic glucocorticoids or other immunosuppression, or
biologic immunomodulators
- Significant or active infection: HIV, Hepatitis B and C
- Active cancer or history of cancer within 3 years of screening
- Participation in other study that involved investigational drug or regimens in the
preceding 12 months
- History of delayed or abnormal wound healing
- Delayed graft function
- Chronic illness or prior treatment which, in the opinion of the investigator,
precludes study participation
- Pregnant or breastfeeding or refusal to us birth control
- Inability or unwillingness to comply with study protocol or procedures
- Chronic use of anticoagulants
- Blood transfusion 3 months prior to transplant
- History of non-compliance
We found this trial at
1
site
740 South Limestone Street
Lexington, Kentucky 40536
Lexington, Kentucky 40536
Phone: 859-323-1691
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